Occupational safety assessment of biogenic urea nanofertilisers using in vitro pulmonary, and in vivo ocular models

Nanomaterials (NMs) are now gaining popularity to be used in agriculture as fertilisers to reduce the dose of conventional fertilisers and enhance nutrient use efficiency. Urea has found its application as a conventional nitrogenous fertiliser since long, however, the nutrient use efficiency of the bulk form of urea is low due to issues related to ammonia volatilisation. This study proposes a biogenic synthesis route to develop urea nanoparticles that can be used as nano-fertiliser for better uptake and hence improved nutrient efficiency. Large scale production and widespread application of these nano-fertilisers to the agricultural fields will enhance the direct exposure to workers and farmers. Therefore, the occupational safety evaluation becomes critical. In this study, we report a new method for synthesis of urea nanoparticles (TNU, absolute size: 12.14 ± 7.79 nm) followed by nano-safety evaluation. Herein, the pulmonary and ocular compatibilities of TNU were investigated in vitro and in vivo respectively. The assay for cellular mitochondrial activity was carried out on human lung fibroblasts (WI-38) under varied TNU exposure concentrations up to 72 h. The acute biocompatibility effect, ocular irritation and sub-lethal effects were measured on New Zealand Rabbit. The results show that TNU do not exhibit any cytotoxicity and detrimental cell mitochondrial activity up to the highest tested concentration of 1000 μg/mL and 72 h of testing. The animal experiment results also show that neither acute nor sub-lethal toxic effects can be detected after TNU ocular instillation up to 21 days when tested up to environmentally relevant concentration of 15 μg/mL. These results suggest the occupational safety of biogenic urea nanoparticles and support its application as nanofertiliser.